All information about the visual world is conveyed from the eyes to the visual centers of the brain by retinal ganglion cells (RGCs). The overall objective of the proposed research program is to further our understanding of the functional organization of these neurons using the mouse retina as a model system. The potential advantage of this approach is the possibility of using the tools of molecular biology to engineer animals (commonly referred to as knockouts) which lack specific cellular attributes. Before taking advantage of the knockout technology, it is essential to obtain information about the organizational properties of RGCs in the normal mouse. For this purpose, we will make patch-clamp recordings in conjunction with Lucifer yellow filling of RGCs to document the structural and functionalproperties of wild-type mouse RGCs. As the first specific aim, we will assess the visual receptive field properties of these neurons using an isolated retinal wholemount preparation in order to determine how the morphologically defined RGCsclasses correlate with their salient responses to light. This will provide the first structural/functional information about RGCs in the mouse retina. Specific Aim 2 will document the intrinsic membrane properties of the different classes of RGCs to test the hypothesis that they express different excitable membrane properties. Our preliminary results indicate that only alpha-type cells manifest T-type currents that regulate bursting activity. Specific aim 3will assess the functional properties of RGCs in knockouts lacking nitric oxide (NO), a gas that been suggested to act as a retinal neurotransmitter. As yet,however, little is known about the involvement of NO in the functional organization of the mammalian retina. In the ferret, I have found that increasing NO selectively blocks "Off" responses in retinal ganglion cells, so it will be particularly interesting to assess whether or not On and Off channels are differentially modified in these genetically altered mice. NO has also been implicated in the refinement of early projection patterns in the developing CNS. Specific aim 4 will determine whether this gas acts to regulate the structural properties of ganglion cells. In particular, we will test the hypothesis that NO is required for the normal stratification of ganglion cell dendrites into On and Off sublaminae of theIPL. PERFORMANCE bl I E(S) (organization, city, state) Section of Neurobiology, Physiology&Behavior Division of Biological Sciences Life Sciences Addition University of California Davis, CA 95616 KEY PERSONNEL. See instructions on Page 11. Use continuation pages as needed to provide the required information in the format shown below. Name Organization Role on Project Guo-Yong Wang University of California, Davis Principal Investigator Leo M. Chalupa University of California, Davis Co-Investigator PHS 398 (Rev. 4/98) Page 2 B B Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. CC Principal^^ptigator/Program Director (Last, first, middle): 4^ Wang, Guoyong Type the name of the principal investigator/progre^rairector at the top of each printed page and each conliriua^Wpaga (For type specifications, see instructions or\r\n ip-\a'agnea 6C.)\ RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page , 1 Description,